Abstract

Congenital heart malformation (CHM) is the most common form of congenital human birth anomaly and is the leading cause of infant mortality. Although some causative genes have been identified, little progress has been made in identifying genes in which low-penetrance susceptibility variants occur in the majority of sporadic CHM cases. To identify common genetic variants associated with sporadic non-syndromic CHM in Han Chinese populations, we performed a multistage genome-wide association study (GWAS) in a total of 4,225 CHM cases and 5,112 non-CHM controls. The GWAS stage included 945 cases and 1,246 controls and was followed by 2-stage validation with 2,160 cases and 3,866 controls. The combined analyses identified significant associations (P < 5.0 × 10 -8) at 1p12 (rs2474937 near TBX15; odds ratio (OR) = 1.40; P = 8.44 × 10 -10) and 4q31.1 (rs1531070 in MAML3; OR = 1.40; P = 4.99 × 10 -12). These results extend current knowledge of genetic contributions to CHM in Han Chinese populations.

abstract = "Congenital heart malformation (CHM) is the most common form of congenital human birth anomaly and is the leading cause of infant mortality. Although some causative genes have been identified, little progress has been made in identifying genes in which low-penetrance susceptibility variants occur in the majority of sporadic CHM cases. To identify common genetic variants associated with sporadic non-syndromic CHM in Han Chinese populations, we performed a multistage genome-wide association study (GWAS) in a total of 4,225 CHM cases and 5,112 non-CHM controls. The GWAS stage included 945 cases and 1,246 controls and was followed by 2-stage validation with 2,160 cases and 3,866 controls. The combined analyses identified significant associations (P < 5.0 × 10 -8) at 1p12 (rs2474937 near TBX15; odds ratio (OR) = 1.40; P = 8.44 × 10 -10) and 4q31.1 (rs1531070 in MAML3; OR = 1.40; P = 4.99 × 10 -12). These results extend current knowledge of genetic contributions to CHM in Han Chinese populations.",

author = "Zhibin Hu and Yongyong Shi and Xuming Mo and Jing Xu and Bijun Zhao and Yuan Lin and Shiwei Yang and Zhengfeng Xu and Juncheng Dai and Shandong Pan and Min Da and Xiaowei Wang and Bo Qian and Yang Wen and Juan Wen and Jinliang Xing and Xuejiang Guo and Yankai Xia and Hongxia Ma and Guangfu Jin and Shiqiang Yu and Jiayin Liu and Zuomin Zhou and Xinru Wang and Yijiang Chen and Jiahao Sha and Hongbing Shen",

N2 - Congenital heart malformation (CHM) is the most common form of congenital human birth anomaly and is the leading cause of infant mortality. Although some causative genes have been identified, little progress has been made in identifying genes in which low-penetrance susceptibility variants occur in the majority of sporadic CHM cases. To identify common genetic variants associated with sporadic non-syndromic CHM in Han Chinese populations, we performed a multistage genome-wide association study (GWAS) in a total of 4,225 CHM cases and 5,112 non-CHM controls. The GWAS stage included 945 cases and 1,246 controls and was followed by 2-stage validation with 2,160 cases and 3,866 controls. The combined analyses identified significant associations (P < 5.0 × 10 -8) at 1p12 (rs2474937 near TBX15; odds ratio (OR) = 1.40; P = 8.44 × 10 -10) and 4q31.1 (rs1531070 in MAML3; OR = 1.40; P = 4.99 × 10 -12). These results extend current knowledge of genetic contributions to CHM in Han Chinese populations.

AB - Congenital heart malformation (CHM) is the most common form of congenital human birth anomaly and is the leading cause of infant mortality. Although some causative genes have been identified, little progress has been made in identifying genes in which low-penetrance susceptibility variants occur in the majority of sporadic CHM cases. To identify common genetic variants associated with sporadic non-syndromic CHM in Han Chinese populations, we performed a multistage genome-wide association study (GWAS) in a total of 4,225 CHM cases and 5,112 non-CHM controls. The GWAS stage included 945 cases and 1,246 controls and was followed by 2-stage validation with 2,160 cases and 3,866 controls. The combined analyses identified significant associations (P < 5.0 × 10 -8) at 1p12 (rs2474937 near TBX15; odds ratio (OR) = 1.40; P = 8.44 × 10 -10) and 4q31.1 (rs1531070 in MAML3; OR = 1.40; P = 4.99 × 10 -12). These results extend current knowledge of genetic contributions to CHM in Han Chinese populations.